A new ts donor virus has been constructed for possible use in immunoprophylaxis. This virus contains ts P3 and ts NP genes and is more stable than the ts-1(E) or ts-1A2 donor virus. Intrasegmental complementation was observed with mutants bearing their lesion in the P1 gene. This suggests that this polypeptide has at least two functional domains. Wild-type H1N1 NP gene was observed to suppress the ts phenotype of a ts P1 gene. Certain avian influenza A viruses were found to be attenuated for squirrel monkeys. Hemagglutinin-specific ELISA was used to characterize isotype-specific immunoglobulin response to primary and secondary infection with influenza virus. Local IgA ELISA antibody to HA correlated with resistance to infection with ca vaccine virus. Lymphocytes cytoxic to influenza A virus infected target cells were detected directly in peripheral blood of volunteers undergoing infection with influenza A virus. Lymphocytes producing IgA and IgG antibodies to hemagglutinin were detected in serum and blood of infected volunteers.